1,4-Diazabicyclooctane di-N,N&#39;-quaternized compounds

ABSTRACT

There is disclosed a novel process for the preparation of 1,4-diazabicyclooctane dihydrohalides having the formula ##STR1## wherein each R is independently selected from the group consisting of hydrogen, lower alkyl, aryl, aralkyl, and cycloalkyl, and X is chlorine or bromine, said process comprising heating at a temperature of at least about 100° C. and in a dipolar aprotic solvent certain novel dihaloalkylene diamines. Neutralization of the dihydrohalides provides the corresponding 1,4-diazabicyclooctane free bases. 
     Also disclosed are certain novel 1,4-diazabicyclooctane diammonium dihalides formed as intermediates in the above process and a process for their conversion to the 1,4-diazabicyclooctane dihydrohalides and free bases thereof. 
     The 1,4-diazabicyclo compounds produced in accordance with the invention find particular utility as catalysts in the preparation of polyurethanes from organic polyols and polyisocyanates.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a division of copending application Ser. No. 956,109filed Oct. 30, 1978, now U.S. Pat. No. 4,216,322.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to 1,4-diazabicyclo-[2.2.2]octanes and is moreparticularly concerned with novel processes for their preparation andcertain novel 1,4-diazabicyclooctane diammonium dihalide intermediatecompounds and novel dihaloalkylene diamine precursors therefor.

2. Description of the Prior Art

The outstanding ability of 1,4-diazabicyclo-[2.2.2]octane (also known astriethylenediamine) and related compounds to catalyze the reaction ofisocyanates with polyols to form urethanes and, also, the reactionbetween isocyanates and water to water-blow urethane foams, but longbeen recognized and utilized by those skilled in the polyurethane foamart; see "DABCO Triethylenediamine, Properties, Reactions andApplications", May 1971, Air Products & Chem. Inc., Wayne, Penna.

The commercial preparation of triethylenediamine, in the main, nowrequires the use of high temperature-high pressure type reactions whichare not energy efficient processes. Typical of such processes is thethermal cracking of diethylenetriamine over a silica-alumina catalyst at355°-360° C. (U.S. Pat. No. 2,937,176). Another typical process is thetreatment of various piperazine stocks, including mixtures of reductionproducts from ethanolamine (i.e. aminoethylpiperazine,hydroxyethylpiperazine, diethylenetriamine and the like), with atungsten-aluminum catalyst, or silica-alumina with ammonia at hightemperature (e.g. 378° C.); see U.S. Pat. Nos. 3,056,788, 3,120,526, and3,231,573. Invariably, these methods lead to multi-product mixtureswhich require complex separation procedures including fractionaldistillation.

The preparation of triethylenediamine via ring closure ofN-(β-cyanoethyl)-N'-(β-chloroethyl)piperazine in a low temperatureprocess has been reported; see U.S.S.R. Patent No. 519,416 (C.A. 86,29873y).

It has now been discovered that triethylenediamine and certainderivatives can be prepared in high yields and in a low temperature andenergy efficient process based on simple and readily available ethylenediamines thereby eliminating the need for preparing a piperazinestarting material. Furthermore, the present process gives rise to but asingle product and in a high state of purity thereby obviating the needfor complex and expensive separation procedures required by the priorart methods.

After the present invention was made there has been published (Khim.Geterotsikl. Soedin. 1978, (4), page 548-50, published Apr. 5, 1978) aprocess for the preparation of triethylenediamine by treatment ofN,N'-bis(β-cyanoethyl)ethylene diamine with ethylene oxide to give thediol followed by chlorination to yieldN,N'-bis(β-chloroethyl)-N,N'-bis(β-cyanoethyl)ethylene diamine which iscyclized and decyanoethylated by boiling in dimethylformamide.

SUMMARY OF THE INVENTION

This invention comprises a process for the preparation of a1,4-diazabicyclooctane dihydrohalide having the formula ##STR2## whereineach R is independently selected from the group consisting of hydrogen,lower-alkyl, aryl, aralkyl, and cycloalkyl, and X is selected from thegroup consisting of chlorine and bromine, said process comprisingheating in a dipolar aprotic solvent at a temperature of at least about100° C., a member selected from the class consisting of a dihaloalkylene diamine having the formula: ##STR3## and a1,4-diazabicyclooctane diammonium dihalide having the formula ##STR4##wherein, in each instance, R and X are as defined above and R₁ is anelectron withdrawing group.

The invention also comprises the compounds (II) and (III).

The invention also comprises the process of preparing the free base1,4-diazabicyclooctane compounds (IV) corresponding to thedihydrohalides (I) by neutralization of the latter.

The term "lower-alkyl" means alkyl having from 1 to 8 carbon atoms,inclusive, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl,octyl, and isomeric forms thereof.

The term "aryl" means the radical obtained by removing one nuclearhydrogen atom from an aromatic hydrocarbon having from 6 to 12 carbonatoms, inclusive, such as phenyl, tolyl, naphthyl, biphenylyl, and thelike.

The term "aralkyl" means the radical obtained by removing one alkylhydrogen from an aryl substituted lower-alkane having from 7 to 20carbon atoms, inclusive. Illustrative of aralkyl are benzyl,p-methylbenzyl, p-ethylbenzyl, β-phenylethyl, benzhydryl,naphthylmethyl, and the like.

The term "cycloalkyl" means the radical obtained by removing onehydrogen atom from a ring carbon atom of a cycloaliphatic hydrocarbonhaving from 3 to 8 carbon atoms, inclusive. Illustrative of cycloalkylare cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl,cycloheptyl, cyclooctyl, and the like.

The term "electron withdrawing group" means a group capable ofattracting electrons and is inclusive of --CN, --COOR, --CONH₂, NO₂,SOR, SO₂ R, and --COR wherein R is defined above.

The free base 1,4-diazabicyclo compounds (IV) prepared in accordancewith the present invention are used as intermediates in the preparationof a variety of chemical products. Typically, they form additioncompounds with bromine and iodine which addition compounds are used asgermicides, bleaching agents, or halogenating agents. Quaternary saltsof the diazabicyclo compounds find utility in a number of applications,for example, their mono- and bis-N-phenacyl acid salts possessantibacterial activity.

It is in their role as catalysts that the 1,4-diazabicyclo compoundsfind particular utility. This includes their catalytic function in theproduction of both flexible and rigid polyurethane foams andpolyisocyanurate foams and as room temperature curatives forpolyurethane elastomers. They also play a catalytic role in the dyeingof textiles with reactive dyes.

DETAILED DESCRIPTION OF THE INVENTION

The process in accordance with the present invention can be summarizedin the following reaction scheme. ##STR5##

It will be seen that the formation of the desired diazabicyclooctanedihydrohalide (I) can be accomplished in accordance with the inventioneither by cyclization and dealkylation of the diamine (II) in a singlestep or by first cyclizing the diamine (II) to the intermediatediammonium halide (III) and then dealkylating the latter. The two stepprocess via the intermediate (III) has the advantage that it generallyresults in a higher overall yield of the desired compound (I). As willbe discussed further below the two step process can be carried out bygenerating the intermediate (III) in situ and dealkylating the latterwithout isolation. Alternatively, the intermediate (III) can be preparedand isolated before being subjected to dealkylation.

When the starting diamine (II) is converted in a single step to thedesired product (I) this is accomplished readily by heating the diamine(II) in the presence of a dipolar aprotic solvent at a temperature of atleast about 100° C. until the formation of the desired product (I) hasproceeded to completion. Advantageously the heating is carried out at atemperature of about 100° C. to about 225° C. and preferably thereaction temperature is within the range of about 125° C. to 200° C. Itis presumed that the reaction proceeds through intermediate formation ofcompound (III) followed by dealkylation of the latter but this isoffered by way of explanation only and is not intended to limit thescope of the present invention in any manner whatsoever.

The course of the conversion and the completion thereof can be observedeasily both qualitatively and quantitatively using any convenientanalytical means known to those skilled in the art. A particularlypreferred method is proton or carbon-13 nuclear magnetic resonanceanalysis with the proton resonance being used for the quantitativedeterminations.

Generally speaking, the dihydrohalide (I) will precipitate from thereaction mixture during the course of the reaction. It can be isolatedfrom the reaction mixture by any convenient means known to those skilledin the art, for example, filtration, centrifugation, and the like.

Although not essential, it is convenient to remove overhead distillateduring the course of the heating. This ensures optimum conversion ofdiamine (II) to the desired product (I) and, additionally, represents apurification step. Generally speaking, the combined heating anddistillation is carried out under atmospheric pressure. Primarily, theoverhead distillate consists of solvent and recovered ethylenic compound(V).

The dipolar aprotic solvent employed in the above step can be any one ofthe solvents falling within this classification well known to thoseskilled in the art. Illustrative of this class of solvents are thefollowing: dimethylformamide, dimethylacetamide, formamide,acetonitrile, dimethyl sulfoxide, diethyl sulfoxide, tetramethylurea,hexamethylphosphoramide, N-methylpyrrolidone, tetramethylenesulfone, andthe like. A preferred solvent in this group is dimethylformamide.

In a preferred embodiment of the present process, the starting compound(II) is cyclized in a first step to the intermediate (III) followed bythe dealkylation of compound (III) to compound (I) in a second step.This is accomplished by heating the diamine (II) in the dipolar aproticsolvent at a temperature up to about 95° C., advantageously, from about70° to about 95° C., preferably from about 75° C. to 85° C. for a periodfrom about 1.0 hour to about 4.0 hours. Then the mixture containing thecompound (III) is heated in accordance with the conditions describedabove for converting (II) directly to (I) by heating at a temperature ofat least about 100° C. in the dipolar aprotic solvent. By carrying outthe conversion of all the diamine (II) to compound (III) before going onto (I), final yields are maximized.

In a further preferred embodiment the cyclization of compound (II) tocompound (III) in the dipolar aprotic solvent is carried out in thepresence of an added base to remove the 2 molar proportion of hydrohalicacid which is formed. Although not essential, the removal of thehydrohalic acid in this manner facilitates the conversion to compound(III). The choice of base is not critical and typical bases that can beused are inorganic bases such as calcium carbonate, sodium carbonate,sodium hydroxide, ammonia; organic bases such as triethylamine,tributylamine, and the like. Solvents like dimethylformamide anddimethylacetamide possess enough inherent basicity to remove thehydrohalic acid. A preferred added base is ammonia.

The quantity of base employed is not critical but if optimum conversionsare desired then, advantageously, it is used in at least about a 2 molarproportion per mole of (II).

Generally speaking, compound (III) precipitates from the reactionsolution even when hot. Accordingly, it can be isolated simply byfiltration, if desired, before being converted to the dihydrohalide (I).

Preferably, compound (III) is not isolated but is dealkylated to thedihydrohalide (I) without isolation by heating the reaction mixtureobtained directly from the cyclization step in accordance with theconditions described above for converting diamine (II) directly todihydrohalide (I) by heating at a temperature of at least about 100° C.in the dipolar aprotic solvent.

Alternatively, if the compound (III) has been isolated from the reactionsolution it can be dealkylated to the product (I) or the free basethereof (IV) simply by heating compound (III) in an organic solvent,which need not be a dipolar aprotic solvent, in accordance with thetemperature conditions described above for converting diamine (II)directly to product (I) or by mixing compound (III) with aqueous base toobtain free base (IV).

The organic solvent employed in the conversion of intermediate (III) toproduct (I) can be any solvent known to one skilled in the art to besuitable for carrying out a dealkylation reaction. Typical of theclasses of solvents useful for such a conversion are aprotic solvents,dipolar aprotic solvents, glycols, and the like.

Illustrative of aprotic solvents are benzer toluene, xylene,chlorobenzene, dichlorobenzene, methylene chloride, ethylene dichloride,chloroform, carbon tetrachloride, heptane, pyridine, and the like.

Illustrative of dipolar aprotic solvents are those set forthhereinabove.

Illustrative of glycols are ethylene glycol, diethylene glycol,propylene glycol, dipropylene glycol, triethylene glycol; polyethers forexample, polyoxyalkylene glycols such as polyoxyethylene glycolsprepared by the addition of ethylene oxide to water, ethylene glycol ordiethylene glycol, polyoxypropylene glycols prepared by the addition of1,2-propylene oxide to water, propylene glycol, and the like. The use ofglycols to convert compound (III) to product (I) is particularlypreferred when the free base product (IV) derived from (I) is to be usedutlimately in a glycol solvent as a polyurethane catalyst component.

In a preferred embodiment of the dealkylation of (III) to (I) thediammonium dihalide compound is carried out in the presence of acatalytic amount of a base. Any one of the bases described above can beemployed, as well as a precursor of a base such as an organic aminehydrochloride salt.

The amount of base, as noted above, is only a catalytic amount and isadvantageously from about 0.1 mole to about 0.3 mole per mole ofcompound (III).

In still another embodiment in accordance with the present invention theintermediate diammonium salt (III) is dealkylated to (I) and neutralizedto (IV) all in one step by mixing (III) with aqueous base. Generallyspeaking, this step involves simply mixing together (III) with theaqueous basic solution at room temperature for a short period,typically, about 10 minutes to 60 minutes. Elevated temperatures, up tothe boiling point (100° C.) of water can be employed but are notgenerally necessary. The base employed is not critical. Typically, itcan be any one of the basic materials set forth above. The quantity ofbase employed is not critical but if optimum conversions are desiredthen advantageously, it is used in at least about a 2 molar proportionper mole of (III).

The free base (IV) can be isolated from the solution by any convenientmeans known to one skilled in the art such as distillation, vacuumconcentration followed by trituration with a solvent, and the like.

A particularly preferred method is to carry out the mixing procedurewith the aqueous basic solution in the presence of an organic solventwhich forms an azeotrope with water. Removal of the precipitatedneutralization salts from the water free mixture yields a solution of(IV) which can then be distilled or induced to cause crystallization ofthe product. Exemplary azeotropic solvents are benzene, toluene, hexane,heptane, and the like.

When (I) is obtained by any of the other embodiments of the process inaccordance with the present invention discussed above, itsneutralization to the free base (IV) is simply accomplished using anystandard method known to one skilled in the art for neutralizing thehydrohalide salt of an organic amine to the free base.

The dihalo alkylene diamine compounds (II) which are employed asstarting materials in the process of the invention, may be preparedusing any appropriate means known to those skilled in the art.Illustratively, they can be prepared via the reaction of a one molarproportion of the appropriately substituted ethylene dihalide with a twomolar proportion of the appropriately substituted secondary amine toprovide (II).

In a preferred preparation of the diamines (II) an ethylene diamine (VI)is first alkylated in accordance with standard procedures with at leasta one molar excess of an ethylenic compound (V) to yield thedi-secondary amine (VII) according to the following equation, ##STR6##wherein, in each instance, R and R₁ are as defined above.

The use in the above syntheses of an alkylene diamine analogous to thoseof formula (VI) but having more than two carbon atoms in the chainconnecting the nitrogens, e.g. 1,3-propylene diamine and 1,4-butylenediamine, yields dihalo alkylene diamines analogous to (II) which willnot cyclize when subjected to the process of the present invention.

Accordingly, illustrative of the diamines which can be used to preparethe starting diamines (II) in accordance with the present invention areethylene diamine, 1,2-propylene diamine, 1,2-butylene diamine,1,2-amylene diamine, 1,2-hexylene diamine, 1,2-heptylene diamine,1,2-octylene diamine, 2,3-butylene diamine, and the like;1-phenyl-1,2-ethylene diamine, 1-tolyl-1,2-ethylene diamine,1-phenyl-1,2-propylene diamine and the like; 1-benzyl-1,2-ethylenediamine, 1(β-phenylethyl)1,2-ethylene diamine, and the like; and1-cyclohexyl-1,2-ethylene diamine, 1-cyclohexyl-1,2-propylene diamine,and the like. A preferred group of diamines consists of ethylenediamine, 1,2-propylene diamine, and 2,3-butylene diamine. A particularlypreferred diamine is ethylene diamine.

The above-described alkylation of the diamine (VI) is well known tothose skilled in the art as a cyanoethylation reaction when the organicelectron withdrawing group R₁ is a cyano(-CN) group, and, generallyspeaking, is carried out in accordance with the teaching set forth inOrganic Reactions, Vol. V, p. 79, 1949, John Wiley and Sons, Inc., NewYork.

When the organic electron withdrawing group is other than a -CN groupthen the reaction is commonly known as a Michael type reaction (see ibidVol. 10, p. 179 for methods of carrying out this type of reaction).

The term "electron withdrawing group" as used in respect of the group R₁and as defined above is used herein in the sense well known in the artas a group which causes a polarization of the α,β-ethylenic compound (V)so as to facilitate the addition of an anionic species at the terminalmethylene group; for a discussion of the cyanoethylation and Michaelreaction and representative R₁ groups see Advanced Organic Chemistry:Reactions, Mechanisms, and Structure, pp. 567-569, 1968 by J. March,McGraw-Hill, New York, N.Y.

Illustrative of the compounds (V) are acrylonitrile,α-methylacrylonitrile, α-ethylacrylonitrile, α-propylacrylonitrile,α-butylacrylonitrile, α-amylacrylonitrile, α-hexylacrylonitrile,α-heptylacrylonitrile, α-octylacrylonitrile, α-phenylacrylonitrile, andthe like; acrolein, α-methylacrolein, α-ethylacrolein, α-phenylacrolein,and the like; methylvinyl ketone, ethylvinyl ketone, butylvinyl ketone,hexylvinyl ketone, phenylvinyl ketone, tolylvinyl ketone, and the like;methyl acrylate, ethyl acrylate, phenyl acrylate, α-methylmethacrylate,α-phenylmethacrylate and the like; acrylamide, α-methylacrylamide,α-butylacrylamide, and the like; nitroethylene, α-methylnitroethylene,α-phenylnitroethylene, and the like; methylvinyl sulfone, ethylvinylsulfone, butylvinyl sulfone, octylvinyl sulfone, phenylvinylsulfone, andthe like; methylvinyl sulfoxide, ethylvinyl sulfoxide, butylvinylsulfoxide, phenylvinyl sulfoxide, p-toluenevinyl sulfoxide, and thelike.

A preferred class of compound (V) consists of acrylonitrile,α-methylacrylonitrile, α-ethylacrylonitrile, α-propylacrylonitrile,α-butylacrylonitrile, α-amylacrylonitrile, α-hexylacrylonitrile,α-heptylacrylonitrile, α-octylacrylonitrile, and α-phenylacrylonitrile.

A most preferred compound (V) is acrylonitrile.

The secondary amine (VII) is converted to the corresponding hydroxyethylderivative (VIII) by replacing each amino hydrogen with the hydroxyethylgroup by reacting (VII) with a two molar proportion of ethylene oxide.The use of higher vicinal oxides such as propylene oxide fails to giverise to products which will undergo the process in accordance with thepresent invention. The ethoxylation is performed using standard methodswell known to those skilled in the art.

The novel dihalo alkylene diamines (II) are obtained by the replacementof the hydroxyl groups of (VIII) through chlorination or brominationusing standard methods well known to those skilled in the art forconverting a hydroxyl group to a chlorine or bromine. The actualhalogenation method employed is not critical and any means for carryingout such a conversion may be employed; see Synthetic Organic Chemistryby Wagner and Zook, pp. 89-92, 1953 John Wiley and Sons, Inc., New York,N.Y. for typical halogenation methods. Typical of the chlorinating orbrominating agents which can be used are hydrogen bromide, hydrogenchloride, phosphorus tribromide, phosphorus trichloride, thionylchloride, thionyl bromide, phosphorus oxychloride, phosphorusoxybromide, phosgene and the like.

The preferred halogenating agents in accordance with the presentinvention are the reagents or addition compounds known as Vilsmeierreagents formed from the combination of dimethylformamide and certaininorganic halide reagents such as phosgene, phosphorus oxychloride,thionyl chloride, and the like, simply by mixing the halide reagent andthe dimethylformamide together prior to the introduction of (VIII); amost preferred combination is the one formed between dimethylformamideand phosgene. For a discussion of Vilsmeier type reagents and their usein converting hydroxyl groups to halides see, Dimethylformamide ChemicalUses, pp. 81-85, 1967 by R. S. Kittila, Copyright by E. I. DuPontDeNemours & Co., Wilmington, Del.

The use of a solvent in the chlorination or bromination is optional.Oftentimes the reactants can serve as their own solvents. In a preferredembodiment an organic solvent is employed. Suitable solvent classesinclude aprotic solvents and dipolar aprotic solvents, exemplary membersof which classes are set forth above. The dipolar aprotic solvents arepreferred as a class and the preferred member of this class isdimethylformamide.

Although the chlorinated or brominated product (II) can be isolated fromthe halogenation mixture using standard separation procedures known tothose skilled in the art, in the preferred embodiment in accordance withthe present invention the reaction mixture is used directly in the nextstep without isolation or purification. Accordingly, yields areoptimized and the overall procedure simplified. Additionally, dihaloalkylene diamines having the formula (II) tend to possess vesicantproperties, therefore, human exposure should be minimized.

When the halogenation step has been carried out in a dipolar aproticsolvent the halogenated product can be left in the same solvent for itsconversion to the product (I). In the event that an aprotic solvent wasemployed in the halogenation then a dipolar aprotic solvent is simplyadded to the reaction mixture prior to converting (II) to (I) inaccordance with the present invention.

The following examples describe the manner and process of making andusing the invention and set forth the best mode contemplated by theinventors of carrying out the invention but are not to be construed aslimiting.

EXAMPLE 1

A four-neck 250 ml. reaction flask equipped with a mechanical stirrer,thermometer, addition funnel, gas inlet tube, and a reflux-distillationhead was charged with 50 ml. of dimethylformamide. Under nitrogen and ata temperature below 10° C., a solution of 17 g. (0.172 mole) of phosgenedissolved in 50 ml. of methylene dichloride was added to the stirredcold dimethylformamide over a period of a half hour.

The flask contents were allowed to return to room temperature (below 25°C.) and 19.66 g. (0.0733 mole) ofN,N'-bis(β-hydroxyethyl)-N,N'-bis(β-cyanoethyl)ethylene diaminedissolved in 50 ml. of dimethylformamide was added to the phosgenesolution during stirring over a period of a half hour causing theprecipitation of a solid complex between the diamine, phosgene, anddimethylformamide. Stirring was continued for an additional half hour atroom temperature. Following this, the stirred reaction solution was heldat 80°-85° C. for 5 hours. Initially, the original precipitate dissolvedbut during the heating period another precipitate formed which wasN,N'-bis(β-cyanoethyl)triethylenediammonium dichloride.

The reflux-distillation head was adjusted for distillation and, over ahalf hour period with a pot temperature of 100° to 110° C. and headvapor temperature of 40°-50° (at 760 mm of Hg pressure), there wascollected 43.22 g. of distillate which was analyzed by proton nuclearmagnetic resonance and shown to consist of 99.8% methylene dichloride,0.1% acrylonitrile, and 0.1% dimethylformamide. During the initial phaseof this heating the solid precipitate dissolved and an obviouscrystalline solid reprecipitated. The pot temperature was raised to140°-150° C. with a head temperature of 70°-135° C. and, over a one hourperiod, there was collected 40.73 g. of distillate which was analyzed byproton NMR and shown to consist of 59.6% methylene dichloride, 7.7%acrylonitrile and 32.9% dimethylformamide.

The pot residue was cooled to 80° C. and the solid collected byfiltration; wt., 12.74 g. C-13 NMR analysis showed it to be1,4-diazabicyclo[2.2.2]octane dihydrochloride.

The filtrate was diluted with 200 ml. of diethyl ether. A precipitatewas filtered and dried to yield 11.48 g. of solid. C-13 NMR analysisshowed that the solid consisted of 95% by weight of dimethylaminehydrochloride and 5% 1,4-diazabicyclooctane dihydrochloride.

The total yield of 1,4-diazabicyclooctane dihydrochloride was 93% (basedon the diamine II) along with an 86% yield of dimethylaminehydrochloride and a 60% recovery of acrylonitrile.

The 1,4-diazabicyclooctane dihydrochloride was converted quantitativelyto the free base 1,4-diazabicyclooctane by neutralization of its aqueoussolution with aqueous sodium hydroxide followed by azeotropicdistillation of the water with heptane and filtration to removeinsoluble salts. Concentration of the heptane solution inducedcrystallization of the pure base.

EXAMPLE 2

A 250 ml. flask equipped according to Example 1 was charged with 50 ml.of dimethylformamide and, at a temperature of 5°-10° C. and undernitrogen, there was added over a half hour period with stirring asolution of 17.85 g. (0.18 mole) of phosgene dissolved in 50 ml. ofethylene dichloride. Stirring was continued for 1 hour at 5°-10° C.

At 20°-25° C. a solution of 20.64 g. (0.081 mole) ofN,N'-bis(β-hydroxyethyl)-N,N'-bis(β-cyanoethyl)ethylene diaminedissolved in a mixture of 25 ml. of dimethylformamide and 25 ml. ofdichloroethane was added dropwise to the above described phosgenesolution over a half hour period and the mixture was stirred for anadditional 30 minute period at 20° C. Following this, the stirredreaction mixture was heated for 3.5 hours at 80°-95° C. under nitrogen.Water (0.4 ml.) was added to the hot solution at a temperature of 90° C.to quench the excess phosgene-dimethylformamide complex. Heating of themixture was continued at 90° C. for a further 4.5 hour period and thenit was allowed to cool and stand overnight.

A crystalline precipitate was collected by filtration, washed withmethanol and dried to provide 21.72 g. (92% yield) ofN,N'-bis(β-cyanoethyl)triethylenediammonium dichloride (analyzed by C-13NMR). The filtrate and methanol washings combined were concentrated invacuo to a dark oily solid, wt., 17.89 g. The solid was washed with a1:1 mixture of isopropanol and methylene chloride to yield 4.22 g. ofbrown solid which C-13 NMR analysis showed to be dimethylaminehydrochloride containing some impurities. Concentration of the filtrateto 13.67 g. of impure solids and C-13 NMR showed it to be predominantlydimethylamine hydrochloride.

The N,N'-bis(β-cyanoethyl)triethylenediammonium dichloride wasrecrystallized from hot aqueous ethanol to yield fine needles, m.p.317°-318° C. (dec.) which contained a half mole of water by hydration,and had the following analysis

Calc'd. for C₁₂ H₂₀ N₄ Cl₂.1/2 H₂ O: C, 48.00%; H 7.38; N, 18.66%; Cl,23.61%. Found: C, 47.82%; H, 7.36%; N, 18.42%; Cl, 23.37%.

Converting N,N'-Bis(β-cyanoethyl)triethylenediammonium Dichloride toTriethylenediamine Dihydrochloride or Free Base Thereof

(a) A 334 mg. sample of the pure diammonium dichloride was mixed with 2ml. of diethyleneglycol and heated to 140° C. causing the salt todissolve. After heating the solution (to or) at 200° C. for 20 min.under atmospheric pressure a distillate was obtained with a boilingrange of 80°-120° C., which distillate was shown by C-13 NMR to containa combination of acrylonitrile and ethylene glycol. The pot residue wasanalyzed by C-13 NMR and shown to contain triethylenediaminedihydrochloride mixed with acrylonitrile.

(b) A suspension of 5.82 g. (0.02 mole) of the diammonium dichloride ina solution of 0.54 g. (0.0066 mole) of dimethylamine hydrochloride in 25ml. of dimethylformamide was heated to 150° C. for 2.5 hours. Thereaftera 3.37 g. distillate was collected boiling at 70°-150° C. underatmospheric pressure. Analysis of the distillate by proton nuclearmagnetic resonance showed it to consist of a mixture of 1.48 g. ofdimethylformamide, 0.3 g. water, and 1.55 g. (0.029 mole) ofacrylonitrile (73% recovery).

The reaction residue was cooled and filtered to yield 2.89 g. (78%yield) of triethylenediamine dihydrochloride which was characterized byboth proton and C-13 NMR.

(c) A 2.91 g. (0.01 mole) sample of the diammonium dichloride was addedto a two phase liquid system consisting of 0.8 g. (0.02 mole) of sodiumhydroxide dissolved in 5 ml. of water and 10 ml. of methylene chloride.The two phase system was rapidly stirred together at room temperaturefor a few minutes. The stirring was stopped and the two layers allowedto separate.

The aqueous phase was washed with 3×10 ml. portions of methylenechloride while the organic phase was washed with 10 ml. of water andthis water wash combined with the aqueous phase. The aqueous solutionwas heated in a Dean-Stark trap with 25 ml. of toluene and the waterremoved by azeotropic distillation. The dry toluene solution wasfiltered to yield 7.95 g. of clear solution which contained 0.55 g. (50%yield) of triethylenediamine by C-13 NMR.

EXAMPLE 3

A four-neck 250 ml. reaction flask equipped according to Example 1 wascharged with 50 ml. of dimethylformamide and at a temperature of 5°-10°C. and under nitrogen there was added over a half hour period duringstirring a solution of 15.19 g. (0.153 mole) of phosgene dissolved inmethylene dichloride. The viscous solution was stirred for 45 minutes at5°-10° C.

A solution of 16.62 g. (0.065 mole) ofN,N'-bis(β-hydroxyethyl)-N,N'-bis(β-cyanoethyl)ethylene diaminedissolved in 50 ml. of dimethylformamide was added dropwise to thephosgene solution (obtained as described above) over a 15 minute periodat 15°-25° C. Stirring was continued for a further period of 15 minutesand then the temperature was raised to 85° C. causing some methylenedichloride to distil over to a receiver. Heating was continued for 1.25hours and then 0.9 g. (0.05 mole) of anhydrous ammonia was added via thegas inlet tube. Heating was continued at 85° C. for 30 minutes andanother 0.9 g. portion of ammonia added. After another 30 minute heatingperiod another 0.9 g. of ammonia was added representing a total additionof 0.15 mole of ammonia. The reaction mixture was then heated for 2hours at 85° C. before being left to stand under nitrogen overnight atambient temperature.

The mixture was heated to 150°-155° C. and overhead distillation ofliquid started. At a pot temperature of 90°-120° a fraction boiling at55° C. and weighing 53.66 g. was obtained. NMR analysis of this fractionidentified the constituents as 97.5% methylene dichloride and 2.5%dimethylformamide.

At a pot temperature of 120°-155° C. a fraction boiling at 55°-145° C.and weighing 28.9 g. was collected and analyzed by NMR to consist of11.0 g. methylene chloride, 12.4 g. dimethylformamide, and 5.5 g.acrylonitrile (80% recovery of the theoretical amount). Heating wasstopped when the head vapor temperature reached 145° C.

When the reaction mixture cooled, a crystalline solid, which had formedpreviously, was isolated by filtration. The collected solid was washedwith dimethylformamide followed by 50 ml. of methanol. It was dried to16.5 g. of light brown powder. Analysis by NMR showed the solid to be amixture of 5.1 g. (0.095 mole) of ammonium chloride and 11.4 g. (0.061mole) of triethylenediamine dihydrochloride.

The filtrate was concentrated in vacuo to 4.8 g. of semisolid residuewhich NMR analysis showed to consist of dimethylformamide and 20-30%dimethylamine hydrochloride plus unidentified by-products.

The 16.5 g. mixture of ammonium chloride and triethylene diaminedihydrochloride obtained above was added in portions to a stirredsolution of 10.0 g. (0.25 mole) of sodium hydroxide in 10.3 g. of water.An additional 8.3 g. of water was added to ensure complete solutionfollowed by 75 ml. of heptane and the immiscible mixture heated toreflux using a Dean-Stark trap to remove water by azeotropicdistillation. A 23.45 g. aqueous fraction collected from the trapcontained 1.69 g. of triethylenediamine by NMR analysis.

The heptane solution was filtered to remove the solid sodium chloride.The solid was washed with 3×25 ml. portions of hot heptane and thewashings added to the main heptane solution. The heptane wasconcentrated by distillation with 87.7 g. of distillate containing 0.12g. of triethylenediamine. The pot residue was cooled andtriethylenediamine crystallized as white prisms. The crystalline productwas collected by filtration and dried to yield 3.36 g. of product whilethe mother liquor contained an additional 0.73 g. of product.

The 5.9 g. total yield of pure triethylenediamine amounted to a 79%overall yield from the startingN,N'-bis(β-hydroxyethyl)-N,N'-bis(β-cyanoethyl)ethylenediamine.

EXAMPLE 4

A 250 ml. flask equipped according to Example 1 was charged with 50 ml.of dimethylformamide, and at a temperature of 5°-10° C. under nitrogen,there was added, over a half hour period with stirring, a solution of15.22 g. (0.153 mole) of phosgene dissolved in 50 ml. of methylenedichloride.

At 20°-25° C. a solution of 16.5 g. (0.062 mole) ofN,N'-bis(β-hydroxyethyl)-N,N'-bis(β-cyanoethyl)-1,2-propylene diaminedissolved in 50 ml. of dimethylformamide was added, over a half hourperiod, to the above solution of phosgene. Following this, the mixturewas heated at 85° C. with constant stirring for 1.5 hours. Then thetemperature was raised first to 110° C. and, over a 1.75 hour period,held at about 150° C. Over the whole 3.25 hour heating period overheaddistillate was collected. The first 45.82 g. fraction was 99% methylenechloride while the second 14.9 g. fraction contained 45% by weight ofacrylonitrile (analyzed by proton NMR).

The reaction mixture was cooled and a solid residue collected byfiltration. The crystalline solid so obtained was washed withisopropanol followed by ether and dried to yield 4.9 g. of off-whitecrystals. C-13 NMR showed the solid to be2-methyl-1,4-diazabicyclo[2.2.2]octane dihydrochloride; yield 40%.Comparison of this C-13 NMR with that of an authentic sample showed thepresent sample to be purer. A further 5.90 g. of crystalline solid wascollected from the filtrate after standing overnight. This was analyzedby proton NMR and found to be a 9:1 by weight mixture of dimethylaminehydrochloride and 2-methyl-1,4-diazabicyclo[2.2.2]-octanedihydrochloride. This additional crop of product raised the total yieldto 45% while the yield of dimethylamine hydrochloride was 52.6%.

I claim:
 1. A 1,4-diazabicyclooctane diammonium dihalide having theformula ##STR7## wherein each R is independently selected from the groupconsisting of hydrogen, lower-alkyl, aryl, aralkyl, and cycloalkyl, andX is chlorine or bromine.
 2. A compound according to claim 1 wherein Rin each case is hydrogen and X in each case is chlorine, said compoundbeing N,N'-bis(β-cyanoethyl)-1,4-diazabicyclo-[2.2.2]octane diammoniumdichloride.